Inhibition of electron transfer by 3-alkyl-2-hydroxy-1,4-naphthoquinones in the ubiquinol-cytochrome c oxidoreductases of Rhodopseudomonas sphaeroides and mammalian mitochondria. Interaction with a ubiquinone-binding site and the Rieske iron-sulfur cluster.
3-Alkyl-2-hydroxy-1,4-naphthoquinones (alkyl-HNQ) inhibit Rieske iron-sulfur cluster (Rieske FeS) oxidation and cytochrome b reduction in ubiquinol-cytochrome c oxidoreductase. The effects are the same as those of 5-undecyl-6-hydroxy-4,7-dioxobenzothiazole. Concentrations for 50% inhibition in chromatophores of Rhodopseudomonas sphaeroides (at 0.4 microM reaction center) are 2 microM for undecyl-, 3 microM for octyl-, and 40 microM for pentyl-substituted hydroxynaphthoquinones. The ethyl-substituted and unsubstituted derivatives do not inhibit electron transfer below 2 mM. In chromatophores in which the ubiquinone is partially extracted by isooctane (leaving 4 ubiquinones/reaction center), undecyl-HNQ is effective at 2.5 times lower concentration than in normal chromatophores (30 ubiquinones/reaction center). This observation suggests that the binding of the inhibitor is competitive with ubiquinone. Undecyl-HNQ eliminates the effect that the ubiquinone redox state has on the line shape of the EPR signal of Rieske FeS. This supports the idea that alkyl-HNQ shares a common binding site with ubiquinone which is closely associated with Rieske FeS. The ubiquinone in question has a midpoint oxidation-reduction potential at pH 7 of 90 mV with a -60 mV/pH unit dependency. This value matches that of the ubiquinone pool rather than that of ubiquinone Z, which is functionally recognized as a component "between" cytochrome b and Rieske FeS. When Rieske FeS is oxidized, a 20 times higher concentration of undecyl-HNQ is required for the electron transfer inhibition. This is consistent with the observation that the binding of the inhibitor shifts the midpoint oxidation-reduction potential of Rieske FeS about 60 mV higher, which in turn means that the inhibitor binds about 10 times stronger to the site when Rieske FeS is reduced than when it is oxidized. The observations suggest that 3-alkyl-2-hydroxy-1,4-naphthoquinones inhibit electron transfer by acting as ubiquinone antagonists at a site closely associated with Rieske FeS.[1]References
- Inhibition of electron transfer by 3-alkyl-2-hydroxy-1,4-naphthoquinones in the ubiquinol-cytochrome c oxidoreductases of Rhodopseudomonas sphaeroides and mammalian mitochondria. Interaction with a ubiquinone-binding site and the Rieske iron-sulfur cluster. Matsuura, K., Bowyer, J.R., Ohnishi, T., Dutton, P.L. J. Biol. Chem. (1983) [Pubmed]
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